On December 30, 2009, Brandon and Gerald Laird were arrested during a fight at US Airways Arena during a Phoenix Suns-Boston Celtics game; Brandon was charged with disorderly conduct.

Brandon made his major league debut at 3B for the Yankees on July 22, 2011, taking over for SS Derek Jeter while 3B Eduardo Nunez moved to short. He walked in his first plate appearance, then got a hit, drove in a run and scored one in a 17-7 Yankee win over the Oakland Athletics. He spent parts of three seasons in the majors, hitting .197/.255/.370, with 6 HR in 127 AB.

Laird signed with the Nippon Ham Fighters for 2015 and hit .231/.301/.488. His 34 homers tied Yuki Yanagita for third in the Pacific League and his 97 RBI were 5th (between Dae-ho Lee and Nobuhiro Matsuda). In 2016, he did better at .263/.319/.516 with 39 home runs and 97 RBI. He won the PL home run title by 4 over Ernesto Mejia, was 4th in RBI (between Mejia and Alfredo Despaigne) and 2nd in slugging (.007 behind Yanagita). In the 2016 Japan Series, he starred, getting Nippon Ham's first run, a solo shot off Kris Johnson in the opener, then hit a two-run blast against Jay Jackson in the bottom of the 8th of game 4 with a 1-1 score to allow the Fighters to even the Series. In game 6, his grand slam off Jackson capped the scoring to give him 3 homers and 7 RBI for the Series. He and Haruki Nishikawa became the first teammates to both hit grand slams in the same Japan Series. He was named Japan Series MVP, the first American to win since Troy Neel 20 years prior.